complement activation, classical pathway

Definition

Target type: biologicalprocess

Any process involved in the activation of any of the steps of the classical pathway of the complement cascade which allows for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes. [GOC:add, ISBN:0781735149]

The classical pathway of complement activation is triggered by the binding of C1q, the first component of the complement system, to immune complexes containing antibodies (IgG or IgM) bound to antigens. This binding initiates a cascade of proteolytic events leading to the formation of the membrane attack complex (MAC), a pore-forming structure that ultimately results in the lysis of target cells.

Here is a step-by-step description of the classical pathway:

1. **C1q Binding:** C1q, a multimeric protein with globular heads, binds to the Fc portion of antibodies bound to antigens. This binding requires at least two antibody molecules in close proximity, typically in the form of an immune complex.

2. **C1r Activation:** The binding of C1q to an immune complex triggers a conformational change in the C1 complex, activating C1r, a serine protease.

3. **C1s Activation:** Activated C1r then cleaves and activates C1s, another serine protease within the C1 complex.

4. **C4 Cleavage:** Activated C1s cleaves C4, a complement protein, into two fragments: C4a and C4b. C4b binds to the cell surface near the antibody-antigen complex, forming a C4b-antigen complex.

5. **C2 Cleavage:** C1s also cleaves C2, another complement protein, into C2a and C2b. C2a binds to C4b, forming a C4b2a complex, known as the classical pathway C3 convertase.

6. **C3 Cleavage:** The C3 convertase cleaves C3, a central component of the complement system, into C3a and C3b. C3b binds to the cell surface, forming a C4b2a3b complex, also known as the classical pathway C5 convertase.

7. **C5 Cleavage:** The C5 convertase cleaves C5, another complement protein, into C5a and C5b.

8. **MAC Formation:** C5b binds to the cell surface and initiates the assembly of the membrane attack complex (MAC). C6, C7, C8, and multiple copies of C9 bind to C5b, forming a pore in the cell membrane. This pore disrupts the cell membrane, leading to cell lysis.

9. **Anaphylatoxins:** The cleavage products C3a and C5a are known as anaphylatoxins, which trigger inflammatory responses by binding to specific receptors on mast cells, basophils, and neutrophils.

The classical pathway is an important part of the innate immune system, providing a rapid and effective defense against pathogens. It is also involved in the clearance of immune complexes and the regulation of immune responses.'
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Proteins (6)

Compounds (12)